The Role of MicroRNA as Clinical Biomarkers for Breast Cancer Surgery and Treatment

Abstract

Breast cancer is the most common cancer diagnosed in women. In recent times, survival outcomes have improved dramatically in accordance with our enhanced understanding of the molecular processes driving breast cancer proliferation and development. Refined surgical approaches, combined with novel and targeted treatment options, have aided the personalisation of breast cancer patient care. Despite this, some patients will unfortunately succumb to the disease. In recent times, translational research efforts have been focused on identifying novel biomarkers capable of informing patient outcome; microRNAs (miRNAs) are small non-coding molecules, which regulate gene expression at a post-transcriptional level. Aberrant miRNA expression profiles have been observed in cancer proliferation and development. The measurement and correlation of miRNA expression levels with oncological outcomes such as response to current conventional therapies, and disease recurrence are being investigated. Herein, we outline the clinical utility of miRNA expression profiles in informing breast cancer prognosis, predicting response to treatment strategies as well as their potential as therapeutic targets to enhance treatment modalities in the era of precision oncology.

Ki-67 as a Prognostic Biomarker in Invasive Breast Cancer

“…First described by Lee et al in 1993 [145], miRNAs have a key role in cancer proliferation, with the clinical utility of prognostic, diagnostic and therapeutic avenues being explored through measuring miRNA expression profiles [146,147]. Increased Ki-67 correlates with aggressive, highly proliferative disease, and efforts have been made to augment Ki-67 indices through supplementation with miRNA expression data: Sakurai et al performed hierarchical cluster analyses to elicit correlations between low, intermediate, and high levels of Ki-67 expression and miRNA expression [148]. Low Ki-67 expression was considered with scores of 0-14% (control group), and nine miRNAs were overexpressed in this group: miR-let-7a, miR-let-7b, miR-let-7e, miR-29a, miR-143, miR-181a, miR-214, miR-218, and small non-coding molecule, SNORD48.…”

“…This is unsurprising as the let-7 family is recognised as being involved in cancer differentiation [149]. Of note, Sakurai et al illustrated miR-21, miR-96, and miR-125b to overlap into a group expressing increased HER2 positivity and Ki-67 [148]. On the contrary, miR-let-214 and miR-15a were expressed in low HER2-expressing cancers, as well as the low Ki-67 group, while miR-27a, miR-92a, miR-301a, miR-355a, and miR-16 were abundant within low HER2expressing tumours, yet overexpressed in cancers with high Ki-67 expression.…”

MicroRNAs in Molecular Classification and Pathogenesis of Breast Tumors

“…Since the first report by Lee et al, deciphering the role of microRNAs in the developmental stages of an entirely different species, Caenorhabditis elegans (c. elegans) [ 32 ], translational research has attributed these small endogenous microRNAs with additional potential as clinical biomarkers for the early detection of breast tumors [ 33 ], as predictors of outcomes of treatment and surgery [ 34 ], and they are also associated with the risk of distant metastasis [ 35 ]. The biogenesis of microRNAs is initiated in the nucleus, from the non-coding regions of DNA harboring the miRNA genes, which undergo transcription to generate 1000-nt-long poly-adenylated primary miRNA transcripts (pri-miRNAs) [ 36 ].…”

MicroRNA Expression Profiles and Breast Cancer Chemotherapy

“…MiRNAs are a contemporary class of small (19–25 nucleotides in length) non-coding endogenous RNAs which are known to play key modulatory roles in gene expression and cellular processes [ 14 ]. They were first described by Lee et al in 1993 when studying developmental timing of Caenorhabditis elegans [ 15 ]; scientific understanding of the role of miRNA has exponentially grown in recent years, with aberrant miRNA expression profiles now understood to correlate with several diverse pathological processes, including oncogenesis [ 70 , 71 ].…”

“…Micro ribonucleic acids (microRNA or miRNA) are small, non-coding ribonucleic acids (RNA) which are key in regulating gene expression [ 14 ]. First described by Lee et al in 1993 [ 15 ], miRNAs have a key role in cancer proliferation, with the clinical utility of prognostic, diagnostic, and therapeutic avenues being explored through measuring miRNA expression profiles [ 16 ].…”